This invention relates to membrane electrodes and, more particularly, to electrodes for use in potentiometric or polarographic assays for non-ionic species.
The ability to accurately and rapidly measure the concentration of various non-ionic species in aqueous media is oftentimes critically important, particularly in situations requiring the monitoring of the concentration of a non-ionic component of a patient's blood. A primary example is the need for monitoring blood glucose levels in diabetic patients requiring insulin injections for control of the disease in proper dosage which is dependent upon the blood glucose level.
In diabetic patients, checking for spill of glucose into the urine and spot blood glucose determinations on an out-patient basis may not provide sufficient information to bring glucose back under control. Furthermore, determination of glucose spill into the urine can sometimes lead to an erroneous judgment about the patient's current insulin requirement. To evaluate and successfully treat this patient, the physician must obtain frequent blood glucose determinations. Frequent blood glucose determination is also desirable when a diabetic patient is acutely ill, undergoing major surgery or childbirth, or suffering from severe keto-acidosis.
Numerous attempts to provide a bedside instrument suitable for continuous glucose monitoring have been made. For the most part, these instruments have required withdrawal of a blood sample from the patient's body, and have not been suitable for implantation for continuous in vivo glucose monitoring. While some of these instruments have employed electrochemical sensors for measuring blood glucose concentration as a function of potentiometric or polarographic response, such sensors have relied upon electrochemical systems which provide only an indirect measurement of glucose concentration. Direct electrochemical measurement of glucose concentration has thus far not been possible. The problems encountered with all of these various previously proposed continuous glucose monitoring instruments have included clotting, non-linearity of the signal output, and drift in the blood sampling and detector systems.
The development of an implantable glucose sensor for the continuous in vivo monitoring of glucose concentration in blood or interstitial fluid without the need for withdrawal of body fluids, and which provides a signal which represents a direct measurement of glucose concentration, should lead to a marked improvement in clinical management and scientific understanding of diabetes. The availability of such a sensor with long-term stability could provide a continuous input for an implanted glucose-controlled glucagon and insulin delivery system, thus aiding greatly in re-establishing and maintaining normal blood glucose levels in the acutely uncontrolled diabetic patients. In addition, such a continuous in vivo sensor would make it much more feasible to conduct a study to determine what influence fluctuation of blood glucose concentration may have on the development of the well-known complications of diabetes.
A recently developed type of electrochemical sensor which has many of the characteristics rendering it potentially suitable for implantation and continuous in vivo monitoring of concentrations of various blood components, is a membrane electrode which is commonly referred to as a "coated wire" electrode. Ion-selective coated wire electrodes are described in detail in the Freiser, et al., U.S. Pat. No. 4,115,209 issued Sept. 19, 1978, incorporated herein by reference to the extent that it is pertinent. In the coated wire-type ion-selective membrane electrode, an ion-selective polymeric membrane is formed as a layer on a conductive substrate, for example, by forming the membrane as a coating directly on the conductive substrate, which is typically in the form of a conductive wire, thereby eliminating the internal reference electrode element employed in the more conventional barrel-type membrane electrodes. The ion-selective polymer membrane is composed of a polymeric matrix having dispersed or dissolved therein a suitable ion-exchange material, i.e., a cation exchange material for cation sensitivity, and an anion exchange material for anion sensitivity. By proper selection of the ion exchange material in the membrane component of the electrode, the electrode may be rendered capable of selectively sensing one or more species of cations or anions present in a test solution. The membrane electrodes described by Freiser, et al., are limited in their utility to the measurement of concentrations of ionic species in test solutions, and are not applicable to non-ionic species.